Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects
The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been report...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1159 |
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| author | Gianluca Caridi Francesca Lugani Andrea Angeletti Monica Campagnoli Monica Galliano Lorenzo Minchiotti |
| author_facet | Gianluca Caridi Francesca Lugani Andrea Angeletti Monica Campagnoli Monica Galliano Lorenzo Minchiotti |
| author_sort | Gianluca Caridi |
| collection | DOAJ |
| description | The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare condition |
| first_indexed | 2024-03-09T23:50:02Z |
| format | Article |
| id | doaj.art-d240e21d55584ed3b05a8d00adaa8a6d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:50:02Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d240e21d55584ed3b05a8d00adaa8a6d2023-11-23T16:36:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233115910.3390/ijms23031159Variations in the Human Serum Albumin Gene: Molecular and Functional AspectsGianluca Caridi0Francesca Lugani1Andrea Angeletti2Monica Campagnoli3Monica Galliano4Lorenzo Minchiotti5UOC Nefrologia e Trapianto Rene, Laboratorio di Nefrologia Molecolare, Istituto Giannina Gaslini IRCCS, 16147 Genova, ItalyUOC Nefrologia e Trapianto Rene, Laboratorio di Nefrologia Molecolare, Istituto Giannina Gaslini IRCCS, 16147 Genova, ItalyUOC Nefrologia e Trapianto Rene, Laboratorio di Nefrologia Molecolare, Istituto Giannina Gaslini IRCCS, 16147 Genova, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyThe human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare conditionhttps://www.mdpi.com/1422-0067/23/3/1159genetic variantsstructural changesstability: ligand bindingpharmacokineticscongenital analbuminaemia |
| spellingShingle | Gianluca Caridi Francesca Lugani Andrea Angeletti Monica Campagnoli Monica Galliano Lorenzo Minchiotti Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects International Journal of Molecular Sciences genetic variants structural changes stability: ligand binding pharmacokinetics congenital analbuminaemia |
| title | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
| title_full | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
| title_fullStr | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
| title_full_unstemmed | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
| title_short | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
| title_sort | variations in the human serum albumin gene molecular and functional aspects |
| topic | genetic variants structural changes stability: ligand binding pharmacokinetics congenital analbuminaemia |
| url | https://www.mdpi.com/1422-0067/23/3/1159 |
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